Cathrin Kodde

Introduction: Pulmonary manifestations of COVID-19 range from asymptomatic cases over severe acute lung injuries such as ARDS to pulmonary long-COVID manifestations. In addition to hyperinflammation, fibrotic lung changes may occur, whose pathogenesis is not yet fully understood. Aims and objectives: The aim of our pilot study was to characterize differences of fibrosis-associated pathways in patients with acute COVID-19 ARDS and long-COVID-ILD compared to non COVID-19 ARDS and other ILD, respectively. Methods: We performed comprehensive transcriptome analyses for RNA sequencing (TruSeq-RNA Kit, Fa. Illumina) on 18 formalin-fixed, paraffin-embedded (FFPE) lung samples (autopsy/intraoperative tissue samples, lung biopsies) from patients with COVID-19 ARDS +/- invasive ventilation and long-COVID-ILD compared to 30 control samples from non COVID-ARDS, NSIP, COP, IPF and healthy lung tissue. Results: In general, transcriptome analyses on FFPE material were challenging due to RNA denaturation. Both homologous and significantly differentially regulated gene expression patterns were identifiable relating to specific fibrosis pathways in COVID-19, non COVID-ARDS, COP and NSIP (see Figure 1). Conclusions: Our preliminary transcriptome analyses suggest distinct gene expression patterns in the various subgroups and may set the basis for future molecular biological studies to understand specific lung fibrosis pathways.

Background: For the last decades, bacteria with multiple resistances to antibiotics (multidrug-resistant organisms, MDRO) are on the rise globally. It is estimated that 700.000 people die each year from MDRO (WHO). Aims: Few data have been published on the role of patients9 gender in MDRO infection, indicating that males may be affected more often. The aim of our study was to determine risk factors and the odds of males with respect to respiratory infection with MDRO in comparison to females. Methods: Surveillance data on MDRO-infections and colonisations collected from 2015 to 2020 in 86 hospitals of the Helios Group, Germany was analysed. We stratified patient’s data according to sample localisation (respiratory, bloodstream, urine, skin/soft tissue sample), age and gender. Results: Out of 7.081.708 patients, 33.023 patients had a detected MDRO-infection of which 2.202 were from respiratory samples. The proportion of males (n=18.310) among the positive study population was higher than that of females (n=14.713; p<.001). Men had significantly more infections detected than women in all sample sites with increasing age, especially in respiratory samples (male:1596, female:606, p<.001). Highest incidence of MDRO respiratory infections were reported among males between 71-75 years (87.9/100.000 patients; OR.441; 95%CI 0.273-0.347). Mostly Methicillin-resistant Staphylococcus aureus, followed by Pseudomonas aeruginosa and Escherichia Coli were found. Conclusions: In our wide-ranged investigation, we showed that among patients with MDRO respiratory infections more males than females were found. The high vulnerability of men to MDRO should be emphasized and studied further.

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.

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.

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.

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.