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 (preprint)

Background: The SARS-CoV-2 variant of concern B.1.1.529 (Omicron) was first described in November 2021 and soon became the dominant variant worldwide. Existing data suggests a reduced disease severity in comparison to B.1.617.2 (Delta). Differences in characteristics and in-hospital outcomes of patients with COVID-19 in Germany during the Omicron period compared to Delta are not thoroughly studied. Surveillance for severe acute respiratory infections (SARI) 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 61.6 vs. 47.8; 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 8.2 vs. 5.4; p<0.01). Comparing Delta and Omicron periods, patients were at significantly lower risk for intensive care treatment (adjusted odds ratio 0.64 [0.51-0.8]; p<0.001), mechanical ventilation (adjusted odds ratio 0.38 [0.28-0.51]; p<0.001), and in-hospital mortality (adjusted odds ratio 0.42 [0.32-0.56]; p<0.001). This also applied to the separate COVID-SARI group. During the Delta to Omicron transition, case numbers of COVID-19 without SARI exceeded COVID-SARI. 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 (preprint)

Background: The aim of our study was to assess the influence of gender and age on reactogenicity by the different vaccines and their combinations. Further parameters were 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 employees of 89 hospitals of the Helios Group. On May 19th, 2021 employees received an invitation by e-mail from the chief medical officer with a link to the survey tool. Participation was voluntary and non-traceable. The survey was closed on June 21st, 2021. Results 8,375 participants reported on 16,727 vaccinations. Reactogenicity was reported in 75% of COVID-19 vaccinations. In 23% the capacity to work was affected. Major risk factors were female gender, younger age and vaccine other than BNT162b2. ChAdOx induced impairing reactogenicity mainly after the prime vaccination (70.5%), while mRNA-1273 led to more pronounced reactions after the second dose (71.7%). Heterologous prime-booster vaccinations with ChAdOx followed by either mRNA-1273 or BNT162b2 were associated with the highest risk for impairment (81.4%). The time of day of the vaccinations showed no influence. Conclusions Young women had the highest chance to experience reactogenicity and to be unable to work after COVID-19 vaccination. When vaccinating a large part of a workforce, especially in professions with a higher proportion of women like health care, employers as well as employees must be prepared for a noticeable amount of absenteeism. 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.

Potential contributors to increased pulmonary embolism hospitalizations during the Covid-19 pandemic (preprint)

Background: After the first Covid-19 infection wave, a constant increase of pulmonary embolism (PE) hospitalizations not linked with active PCR-confirmed Covid-19 has been observed but potential contributors to this observation are unclear. Therefore, we analyzed associations between changes in PE hospitalizations and (1) the incidence of non-Covid-19 pneumonia, (2) the use of computed tomography pulmonary angiography (CTPA), (3) volume depletion and (4) preceding Covid-19 infection numbers in Germany. Methods: Claims data of Helios hospitals in Germany were used and consecutive cases with a hospital admission between May 6 and December 15, 2020 (PE surplus period) were analyzed and compared to corresponding periods covering the same weeks in 2016-2019 (control period). We analyzed the number of PE cases in the target period with multivariable Poisson general linear mixed models (GLMM) including (a) cohorts of 2020 versus 2016-2019, (b) the number of cases with pneumonia, (c) CTPA, and (d) volume depletion and adjusted for age and sex. In order to associate the daily number of PE cases in 2020 with the number of preceding SARS-CoV-2 infections in Germany, we calculated the average number of daily infections (divided by 10,000) occurring 14 up to 90 days with increasing window sizes before PE cases and modelled the data with Poisson regression. Results: There were 2,404 PE hospitalizations between May 6 and December 15, 2020 as opposed to 2,112-2,236 (total 8,717) in the corresponding 2016-2019 control periods. (crude rate ratio [CRR] 1.10, 95% CI 1.05-1.15, P<0.01). Using multivariable Poisson GLMM adjusted for age, sex and volume depletion, PE cases were significantly associated with the number of cases with pneumonia (CRR 1.09, 95 % CI 1.07-1.10, P<0.01), and with CTPA (CRR 1.10, 95 % CI 1.09-1.10, P<0.01). The increase of PE cases in 2020 compared with the control period remained significant (CRR 1.07, 95 % CI 1.02-1.12, P<0.01) when controlling for those factors. In the 2020 cohort, number of preceding average daily Covid-19 infections were associated with increased PE case incidence in all investigated windows, i.e. including preceding infections from 14 to 90 days. The best model (log likelihood -576) was with a window size of 4 days, i.e. average Covid-19 infections 14-17 days before PE hospitalization had a risk of 1.20 (95 % CI 1.12-1.29, P<0.01). Conclusions: There is an increase in PE cases since early May 2020 compared to corresponding periods in 2016-2019. This surplus was significant even when controlling for changes in potential modulators such as demographics, volume depletion, non-Covid-19 pneumonia, CTPA use and preceding Covid-19 infections. Future studies are needed (1) to investigate a potential causal link for increased risk of delayed PE with preceding SARS-CoV-2 infection, and (2) to define optimal screening for SARS-CoV-2 in patients presenting with pneumonia and PE.

Hospitalizations for emergency-sensitive conditions in Germany during the Covid-19 pandemic - Insights from the German-wide Helios hospital network (preprint)

Background: While there are numerous reports that describe emergency care during the early Covid-19 pandemic, there is scarcity of data for later stages. This study analyzes hospitalization rates for 37 emergency-sensitive conditions in the largest German-wide hospital network during different pandemic phases. Methods: Using claims data of 80 hospitals, consecutive cases between January 1 and November 17, 2020 were analyzed and compared to a corresponding period in 2019. Incidence-rate ratios (IRR) comparing the both periods were calculated using Poisson regression to model the number of hospitalizations per day. Results: There was a hospitalization deficit between March 12 and June 13, 2020 (coinciding with the 1st pandemic wave) with 32,807 hospitalizations as opposed to 39,379 in 2019 (IRR 0.83, 95% CI 0.82-0.85, P<0.01). During the following period (June 14 to November 17, 2020, including the start of 2nd wave), hospitalizations were reduced from 63,799 in 2019 to 59,910 in 2020, but this reduction was not that pronounced (IRR 0.94, 95% CI 0.93-0.95, P<0.01). There was an increase in hospitalizations for acute myocardial infarction, aortic aneurism/dissection and pulmonary embolism after the 1st wave during which hospitalizations had been reduced for those conditions. In contrast, hospitalizations for sepsis, pneumonia, obstructive pulmonary disease, and intracranial injuries were reduced during the entire pandemic. Conclusions: There was an overall reduction of hospitalizations for emergency-sensitive conditions in Germany during the Covid-19 pandemic with heterogeneous effects on different disease categories. The increase of hospitalizations for acute myocardial infarction, aortic aneurism/dissection and pulmonary embolism is an alarming signal that requires attention and further studies.

Hospitalizations, resource use and outcomes of acute pulmonary embolism in Germany during the Covid-19 pandemic - Emergence of different phenotypes of thrombotic disease? (preprint)

Background: There is discussion evolving around the emergence of different phenotypes of Covid-19-associated thromboembolic disease, i.e. acute pulmonary embolism vs pulmonary thrombosis and different phenotypes of in situ thrombosis. With this study, we wish to provide hospitalization, treatment and in-hospital outcome data for pulmonary embolism during the 2020 Covid-19 pandemic and a corresponding 2016-2019 control period. Methods: We performed a retrospective analysis of claims data of Helios hospitals in Germany. Consecutive cases with a hospital admission between January 1 and December 15, 2020 and pulmonary embolism as primary discharge diagnosis were analyzed and compared to a corresponding period covering the same weeks in 2016-2019. Results: As previously reported for other emergent medical conditions, there was a hospitalization deficit coinciding with the 1st pandemic wave. Beginning with the 12-week interval May 6 - July 28, there was a stable surplus of hospital admissions in 2020. During this surplus period (May 6 - December 15, 2020), there were 2,449 hospitalizations including 45 PCR-confirmed Covid-19 cases (1.8%) as opposed to 8,717 in 2016-2019 (IRR 1.12, 95% CI 1.07-1.18, P<0.01). When excluding Covid-19 cases IRR was 1.10 (95% CI 1.05-1.15, P<0.01). While overall comorbidities expressed as weighted AHRQ Elixhauser Comorbidity Index (14.1+/-10.1 vs. 13.9+/-10.3, P=0.28), the presence of thrombosis (46.1 vs 45.4%, P=0.55) and surgery (3.8 vs. 4.3%, P=0.33) were comparable, coagulopathy (3.3 vs 4.5%, P=0.01) and metastatic cancer (3.0 vs 4.0%, P=0.03) as contributing factors were less frequently observed during the 2020 surplus. Interventional treatments (thrombolytic therapy, thrombectomy or inferior vena cava filter placement) were less frequently used (4.7 vs 6.6%, OR 0.72, 95% CI 0.58-0.89, P< 0.01). Similarly, intensive care (35.1 vs 38.8%, OR 0.83, 95% CI 0.75-0.92, P< 0.01) and mechanical ventilation utilization (7.2 vs 8.1%, OR 0.88, 95% CI 0.74-1.04, P=0.14) as well as in-hospital-mortality rates (7.8 vs 9.8%, OR 0.76, 95% CI 0.64-0.90, P< 0.01) were lower in 2020 compared with 2016-2019. This was associated with a shorter length of hospital stay (6.4+/-5.4 vs. 7.2+/-5.7 days, P< 0.01) during the 2020 surplus period. Conclusions: Only a minority of cases were associated with PCR-confirmed Covid-19 but this does not rule out preceding or undetected SARS-CoV-2 infection. Although there is a shift towards milder disease course, the increased incidence of hospitalizations for pulmonary embolism requires immediate attention, close surveillance and further studies.