Entfällt - Sonographic assessment of low muscle quantity identifies mortality risk during COVID-19: a prospective single-centre study
Assessment of muscle quantity by sonographic muscle indices could help identify patients at risk for fatal outcome during coronavirus disease-2019 (COVID-19). The aim of this study was to explore sonographic muscle indices as predictors of COVID-19 outcome and to test the feasibility of sonographic muscle measurement in an isolation context.
Muscle indices, derived from the psoas muscle or thigh muscles, were quantified by sonography in a cohort of patients without COVID-19 to obtain reference values for low muscle quantity. Gender-specific median of different muscle indices were defined as threshold value for low muscle quantity. The prognostic relevance of low muscle quantity, was prospectively explored in two cohorts of hospitalized COVID-19 patients. Optimal muscle index cutoff values predictive for 30 day mortality during COVID-19 were determined by receiver operating characteristic-area under the curve and Youden index calculation. Muscle quantity and known prognostic factors of COVID-19 were analysed by multivariable log-regression.
Compared with other muscle indices, the psoas muscle area index (PMAI) showed the most favourable characteristics to predict outcome of COVID-19 disease. Sonographic morphometry of patients without COVID-19 (n = 136) revealed a gender-specific median for PMAI (male: 291.1 mm2/m2, female 260.6 mm2/m2) as threshold value of low muscle quantity. Subsequently, COVID-19 patients (Cohort I: n = 58; Cohort II: n = 55) were prospectively assessed by bedside sonography. The studied COVID-19 patients developed a critical course of disease in 22.4% (Cohort I: n = 13/58) and 34.5% (Cohort II: n = 20/55). Mortality rate reached 12.1% (Cohort I: n = 7/58) and 20.0% (Cohort I: n = 11/55) within 30 days of follow up. COVID-19 patients with a PMAI below the gender-specific median showed a higher 30 day mortality in both COVID-19 cohorts (log rank, P < 0.05). The optimal PMAI cutoff value (206 mm2/m2) predicted 30 day mortality of hospitalized COVID-19 patients with a sensitivity of 72% and specificity of 78.5% (receiver operating characteristic-area under the curve: 0.793, 95% confidence interval 0.671–0.914, P = 0.008). Multivariable log-regression analysis of PMAI, age, gender, BMI and comorbidities confirmed an independent association of low PMAI with 30 day mortality of COVID-19 patients (P = 0.018).
Sonographic morphometry provides reliable muscle quantification under hygienic precautions and allows risk stratification of patients with COVID-19.
Concomitant Administration of the Adjuvanted Recombinant Zoster Vaccine (RZV) with 13-Valent Pneumococcal Conjugate Vaccine (PCV13) Is Safe and Does Not Interfere with Immunogenicity of Either Vaccine in Adults Aged ≥ 50 Years
S. Halwe (München, DE)
This study assessed non-inferiority of humoral immunogenicity, reactogenicity, and safety of RZV when the 1st dose was co-administered with PCV13 in adults ≥ 50 years of age (YOA) compared to sequential administration.
In this phase 3b, open-label, multi-center study (NCT03439657), adults were randomized 1:1 to receive either the 1st RZV dose co-administered with PCV13 at day (D)1 and the 2nd RZV dose at month (M)2 (Co-Ad group), or PCV13 at D1, the 1st RZV dose at M2 and the 2nd RZV dose at M4 (Control group). Co-primary confirmatory objectives were: (i) vaccine response rate (VRR) to RZV at 1 month post-dose 2 in Co-Ad group; (ii) non-inferiority of humoral responses to RZV (1 month post-RZV dose 2) and PCV13 (1 month post-PCV13) in Co-Ad group compared to Control group. Solicited adverse events (AEs) until D7 post-vaccination and unsolicited AEs until D30 post-vaccination were recorded. Serious AEs (SAEs) and potential immune-mediated diseases (pIMDs) were collected through 12 months post-RZV dose 2. Immunogenicity was performed in the per-protocol set (PPS) and safety analyses in the exposed set.
Of 912 vaccinated adults, 863 were included in PPS (Co-Ad: 427; Control: 436). VRR for anti-glycoprotein E antibody concentrations was 99.1% in Co-ad group. The predefined non-inferiority criteria for the humoral immune responses to RZV and PCV13 were met. The overall frequency of solicited local AEs after RZV and PCV13 was comparable between Co-Ad and Control groups. Pain was the most common solicited local AE. The frequency of solicited general AEs was similar for the 1st RZV dose when co-administered with PCV13 or alone (57.4% vs 54.6%). Myalgia and fatigue were the most common solicited general AEs. The frequency (Co-Ad: 21.2%; Control: 23.1%) and nature of unsolicited AEs were balanced between groups. None of the reported SAEs, fatal SAEs, or pIMDs were vaccine-related.
Co-administration of the 1st RZV dose with PCV13 showed non-inferior immune responses to sequential administration. The reactogenicity and safety of RZV in the Co-Ad group were within the range of the established safety profile of RZV. Co-administration of RZV with PCV13 may improve vaccination rates in ≥ 50 YOA population.
Funding: GlaxoSmithKline Biologicals SA (GSK study identifier: 204487)
Acknowledgements: Modis (original abstract – coordinator: Elise Verplanke – Writer: Noemi Bulk) and Business & Decision Life Sciences (ENCORE abstract – coordinator: Julien Doornaert).
NO INCREASE IN HOSPITALISATION SEVEN MONTHS AFTER COVID-19 – YET QUALITY OF LIFE DECLINES
E. Balensiefen (Singen, DE)
J. Haberland (Singen, DE)
M. Kollum (Singen, DE)
For over a hundred years viral pandemics recurrently lead to restrictions of public health. Feared characteristics are prolonged recovery and secondary diseases among the surviving. From a socioeconomic perspective medical measures need to be planned efficiently based on significant data. Despite numerous COVID-19 follow-up studies there is still a lack of knowledge in this field.
The prospective controlled cohort Follow-up Study of COVID-19 cases in the district of Konstanz (FSC19-KN) examined 281 adults with PCR-confirmed SARS-CoV2-infection. Initial visits were performed between January and July 2021 at a mean of seven months after infection. In total 238 age- and gender-matched subjects with corresponding cardiovascular risk profile and negative SARS-CoV-2 antibody titers were recruited as controls. Finally, 206 matching pairs could be established. Frequency of inpatient admission during observational period including related diagnosis was defined as primary endpoint. Secondary endpoints included health-related quality of life measured by European Quality of Life-5-Dimensions-5-Level (EQ-5D-5L) and Short Form Health 36 (SF-36), physical performance during six minute walk test (6MWT) as well as functional outcome estimated via Post COVID Functional Scale (PCFS). Data were given as mean ± standard deviation and difference in means (MD) with 95% confidence interval (CI). Strength of association between two events was quantified by odds ratio (OR) with 95% CI.
SARS-CoV-2 positive subjects were mostly symptomatic (95.1%) but hospitalised only to a small extent (2.4%). Frequency of inpatient admission did not differ significantly between both groups (2.4 % positive group vs. 2.9% controls; OR 0.8 CI [0.2; 2.8]). Relatedness of admission diagnoses to prior infection could not be proven. Results of 6MWT ratio showed no significant difference between both cohorts (0.97±0.17 vs. 0.98±0.16 controls; MD 0.01 CI [-0.04; 0.02]). However, SARS-CoV-2 positive subjects reported reduced quality of life via significantly lower EQ-5D-5L index scores (0.92±0.12 vs. 0.95±0.1 controls; MD -0.03 CI [-0.05; -0.01]) as well as SF-36 physical (54.5±9.0 vs. 57.8±7.0 controls; MD -3.3 CI [-4.9; -1.7]) and mental summary scores (46.3±11.7 vs. 51.9±9.0 controls; MD -5.6 CI [-7.7; -3.5]). Reduced functional outcome (PCFS ≥ 2) was detected significantly more often in the SARS-CoV-2 positive cohort (30.6% vs. 14.5% controls; OR 2.6 CI [1.6; 4.2]).
SARS-CoV2 positive subjects went through mild clinical courses. During first seven months of observation frequency of inpatient admission was identical in both cohorts. Despite good performance in cardiopulmonary exercise SARS-CoV2-positive participants reported reduced quality of life and functional sequelae. Underlying psychoneurological mechanisms need further investigation.
Efficacy and Immunogenicity of an Ad26.RSV.preF-based Vaccine in the Prevention of RT-PCR-confirmed RSV-mediated Lower Respiratory Tract Disease in Adults Aged ≥65 Years: A Randomized, Placebo-controlled, Phase 2b Study
A. Warmeling (Neuss, DE)
Background: Respiratory syncytial virus (RSV) can cause serious lower respiratory tract disease (LRTD) in older adults. Despite a high burden of disease, there is currently no licensed vaccine for RSV. Here, we report the primary efficacy and immunogenicity results from a Phase 2b proof-of-concept trial of an Ad26.RSV.preF-based vaccine for the prevention of RSV-mediated LRTD in adults aged ≥65 years.
Methods: CYPRESS (NCT03982199) is a randomized, double-blind, placebo-controlled Phase 2b trial. Adults ≥ 65 years of age were randomized 1:1 prior to the RSV season to receive an Ad26.RSV.preF-based vaccine or placebo. Symptoms of acute respiratory infection (ARI) were collected through an RSV-specific patient-reported Respiratory Infection Intensity and Impact Questionnaire (RiiQ) and/or by a clinician assessment until the end of the RSV season. The primary endpoint was the first occurrence of RT‑PCR-confirmed RSV-mediated LRTD according to any of 3 case definitions: (1) ≥ 3 symptoms of lower respiratory tract infection (LRTI), (2) ≥ 2 symptoms of LRTI, or (3) ≥ 2 symptoms of LRTI or ≥ 1 symptom of LRTI with ≥ 1 systemic symptom. The secondary endpoint was the first occurrence of any RT‑PCR-confirmed RSV-mediated ARI. Immunogenicity assessments were performed in a subset of approximately 200 participants.
Results: A total of 5782 participants (2891 in each study arm) received study treatment (92.5% white, 57.7% female, median age 71 years). Vaccine efficacy was 80% (94.2% CI, 52.2-92.9%), 75% (50.1-88.5%), and 69.8% (43.7-84.7%) for case definition 1, 2, and 3, respectively (all P values < 0.001). All RSV illnesses met case definition 3 and thus, efficacy for any RSV-mediated ARI was 69.8% (95% CI, 42.7-85.1%). In the vaccine arm of the immunogenicity subset, geometric mean fold increase in antibody titers 14 days after vaccination was 13.5 for RSV neutralizing antibodies and 8.6 for RSV prefusion F-specific binding antibodies. Median frequency of RSV-F-specific INFγ T-cells increased from 34 to 444 SFC/106 PBMC 14 days after vaccination in the vaccine arm; no relevant changes were observed in the placebo arm.
Conclusion: In CYPRESS, the Ad26.RSV.preF-based vaccine was highly effective against RSV-mediated LRTD through the first RSV season and elicited robust humoral and cellular immune responses in adults aged ≥ 65 years.
Q-Fieber als seltene Differentialdiagnose einer schweren Hepatitis unter Immunsuppression
S. Reichermeier (Amberg, DE)
Einleitung: Q-Fieber ist eine weltweit verbreitete Zoonose, verursacht durch das gram-negative Bakterium Coxiella (C.) burnetii. Vögel, Zecken und verschiedene Säugetiere (z.B. Schafe) gelten als mögliche Reservoire. Die Übertragung erfolgt meist durch Inhalation infizierter Aerosole. Als Risikogruppen gelten v.a. Berufsgruppen mit entsprechendem Tierkontakt, z.B. Schlachthauspersonal. Obwohl 50% der Infektionen asymptomatisch verlaufen, kann es bei einer akuten Infektion zu Fieber, Schüttelfrost, Muskelschmerzen bis hin zur interstitiellen Pneumonie oder Hepatitis kommen.
Im vorliegenden Fall konnte bei einem immunsupprimierten Patienten nach umfangreicher Ausschlussdiagnostik eine C. burnetii-Infektion als Ursache einer schweren Hepatitis nachgewiesen werden.
Fallbericht: Die Vorstellung des 79-jährigen, männlichen Patienten erfolgte bei Fieber, Schüttelfrost sowie cholestatischer Hepatitis in unserer Notaufnahme. Der Patient berichtete zudem über Gelenkschmerzen wechselnder Lokalisation sowie über mehrere Zeckenbisse zwei Wochen zuvor. Es bestand eine Immunsuppression mit Mycophenolat und Prednisolon bei Schleimhautpemphigoid. Eine umfangreiche Diagnostik mittels MRT der BWS/LWS, Urinkultur, Blutkulturen und CT des Thorax/Abdomen zeigte keinen Infektfokus. Ebensowenig bestanden Hinweise auf eine Borreliose oder septische Arthritis. Es erfolgte zunächst eine empirische Antibiose mit Piperacillin/Tazobactam. Abdomensonographisch zeigte sich im Verlauf eine intrahepatische Cholestase, so dass bei V.a. obstruktive Cholangitis eine ERCP durchgeführt wurde. Dies bestätigte sich nicht, es erfolgte temporär die Anlage eines Gallengang- und Pankreasstents. Nach Stententfernung kam es zum erneuten Anstieg der Infektparameter mit Nachweis von Klebsiella oxytoca in den Blutkulturen. Unter V.a. Post-ERCP-Cholangitis wurde die Antibiose auf Meropenem eskaliert mit laborchemischem Ansprechen. Parallel zu den genannten Prozeduren erfolgte eine umfangreiche laborchemische Abklärung der Hepatitis. Ausgeschlossen werden konnten etliche infektiöse Ursachen (Hepatitis A, B, C, E, CMV, EBV, HIV, VZV, HSV, Brucellose, Leptospirose) sowie eine Autoimmunhepatitis. Aufgrund des Kontakts zu Zecken wurden ergänzend Serologien bzgl. Q-Fieber, Anaplasmose und Ehrlichiose durchgeführt. Darin ergab sich schließlich ein positiver Befund für C. burnetii IgM (Phase II). Therapie der Wahl bei akuter Q-Fieber-Infektion ist Doxycyclin, allerdings kommt es häufig zur Spontanheilung. Im vorliegenden Fall erreichte uns der positive Antikörpernachweis erst nach Normalisierung der Entzündungs- und Leberwerte und Besserung des Allgemeinzustands, so dass keine spezifische Therapie erfolgte.
Fazit: Insbesondere bei immunsupprimierten Patienten kommen auch seltene Erreger infektiöser Erkrankungen in Betracht. Da C. burnetii v.a. im süddeutschen Raum Verbreitung findet, ist eine Abklärung bei stattgehabtem Kontakt zu entsprechenden Wirten und entsprechender Symptomatik empfehlenswert.
Seroprevalence of SARS-CoV-2-Anti-Spike-IgG antibodies in healthcare workers after vaccination or infection
J. Reusch (Würzburg, DE)
Against the background of the current COVID-19 infection dynamics with the rapid spread of the Omicron variant, the immunity of health care workers against SARS-CoV-2 continues to be of high importance. The humoral immune response, in particular, is being investigated to provide forecasts regarding immunity and protection against severe disease courses; however, the available data is still insufficient to make any concrete statements based on antibody titres.
The aim of our study was to determine the seroprevalence of SARS-Cov-2-Anti-Spike IgG after SARS-CoV-2 infection or vaccination in healthcare workers.
1668 study participants were recruited who met the following inclusion criteria: Age ≥ 18 years, PCR-confirmed SARS-CoV-2 infection and/or vaccination against SARS-CoV-2, working in health care. SARS-CoV-2-Anti-Spike IgG titres were determined by SERION ELISA agile SARS-CoV-2 IgG which shows a high correlation with neutralisation titres with R2 = 0.87 (1). Titres above the threshold of 31.5 BAU/ml indicate at least a moderate neutralisation capacity (2).
77.7% (7/9), 95.1% (1428/1501), and 100.0% (60/60) of participants who had received one, two, and three or four doses of vaccination had antibody titres >31.5 BAU/ml. While 98.8% (83/84) of the participants who had recovered from COVID-19 and were vaccinated had neutralising antibody titres >31.5 BAU/ml, only 92.9% (13/14) of the recovered, non-vaccinated participants had titres >31.5 BAU/ml.
Both recovered and vaccinated participants predominantly present a good humoral immune response. After a third vaccination dose, the titres increased significantly. The temporal course of the titres and possible effects on the incidence of SARS-CoV-2 infections in vaccinated and recovered healthcare workers now need to be investigated.
Immunogenicity and safety of a co-administration of a third SARS-CoV-2 vaccination dose with influenza vaccination
I. Wagenhäuser (Würzburg, DE)
While SARS-CoV-2 booster vaccinations play an important role in strengthening immunoresponse against SARS-CoV-2, a seasonal influenza vaccination has been an important infection prevention measure for years. The aim of our study was to analyse differences in antibody formation and side effects after SARS-CoV-2 booster vaccinations with and without a co-administered influenza vaccination.
751 study participants were recruited, who had received a third SARS-CoV-2-vaccination at least 14 days before participation. SARS-CoV-2-Anti-Spike IgG titres were determined by SERION ELISA agile SARS-CoV-2 IgG and converted to Binding Antibody Units per ml (BAU/ml) according to the First WHO International Standard. SERION ELISA agile SARS-CoV-2 IgG shows a high correlation with titres quantified by plaque reduction neutralisation test (1, 2). Side effects were recorded by an online questionnaire.
Median SARS-CoV-2-Anti-Spike IgG was higher in persons without coadministered influenza vaccination (1803 BAU/ml, IQR: 1136 – 2777 BAU/ml) compared to persons with a coadministered influenza vaccination (1560 BAU/ml, IQR: 1085 – 2484 BAU/ml), but this difference was not statistically significant (p = 0.058).
No significant differences in reported side effects and incapacity to work (mean duration: 0.42 days vs. 0.52 days, p =0.23) could be observed between persons with and without coadministered influenza vaccine.
A third SARS-CoV-2-vaccination dose induced high antibody titres with and without coadministered influenza vaccination. Coadministration of an influenza vaccine does not lead to increased side effects. As influenza vaccination is an important infection prevention measure, coadministration may increase vaccine uptake. The observed insignificantly lower antibody titres have to be analysed in a bigger cohort.
Clinical virus variant specific performance evaluation of SARS-CoV-2 rapid antigen testing in point of care usage in comparison to RT-qPCR
I. Wagenhäuser (Würzburg, DE)
N. Petri (Würzburg, DE)
Rapid antigen tests for SARS-CoV-2 are fast, broadly available and inexpensive. However, previous studies have shown substantial differences in sensitivity and specificity. Published data from a first analysis including 5,171 parallel samples showed a large difference in sensitivity between manufacturers’ data and clinical use (EBioMedicine 2021,69:103455), but virus variant dependency of antigen rapid detection tests (RDT) is a broadly discussed topic.
In this prospective follow-up study, three RDT from three manufacturers (nal von minden NADAL®, Abbott Panbio™, MEDsan®) were compared to quantitative reverse transcription polymerase chain reaction (RT-qPCR). In total, 21,157 oropharyngeal swabs were analyzed. Cycle threshold (Ct) values of all RT-qPCR positive samples were determined.
Overall, the sensitivity of RDTs was 42.86% (95%CI: 35.89%-50.12%) and the specificity 99.69% (95%CI: 99.61%-99.76%). Sensitivity negatively correlated with RT-qPCR derived Ct values. With considerable viral load (Ct ≤ 15), sensitivity was 100.00% and decreased to 75.00% (15 < Ct ≤ 20), 54.55% (20 < Ct ≤ 25), 24.00% (25 < Ct ≤ 30) to 5.00% in samples with a Ct>30. The negative predictive value in the study cohort was 99.51% (95%CI: 99.40%-99.59%), the positive predictive value 54.55% (95%CI: 46.37%-62.48%). No significant differences in sensitivity or specificity could be observed between the three manufacturers and between samples with wild type, alpha, and delta variant.
RDTs are a reliable method to diagnose SARS-CoV-2 infection in patients with a presumable higher viral load independently from spike protein mutations. RDTs may be a valuable addition to RT-qPCR testing as they may detect infectious patients before RT-qPCR results are available and offer the opportunity of broad repeated population testing. Data on antigen rapid test performance regarding the Omicron variant will be presented at the conference.
Health related quality of life is impaired in people living with HIV and hepatic steatosis
M. Michel (Mainz, DE)
Introduction: People living with HIV (PLWH) show a high prevalence of hepatic steatosis and non-alcoholic fatty liver disease (NAFLD). NAFLD has been linked to impaired health-related quality of life (HRQL) and therefore could be an aggravating factor in PLWH. The aim of this study was to determine differences in HRQL between PLWH presenting with and without hepatic steatosis and to identify predictors associated with impaired HRQL.
Methods: A total of 245 PLWH were prospectively enrolled at an outpatient clinic. Hepatic steatosis was assessed using vibration controlled transient elastography (VCTE) and defined as a controlled attenuation parameter (CAP) of > 275 dB/m. The cohort was then divided into two groups: no steatosis and steatosis. The generic EQ-5D-5L questionnaire was used to determine differences in the HRQL. It consists of an overall value (UI-value) and five dimensions, each addressing different aspects of an individual HRQL. Univariable and multivariable linear regression models were applied to identify predictors with impaired HRQL in both groups.
Results: In this cohort of PLWH, the prevalence of hepatic steatosis was 35% (n = 85) of whom 76.5% (n = 65) had NAFLD and 16.5% (n = 14) alcoholic liver disease. The median age was 52 years (IQR 42; 58) and the majority of PLWH were male (n = 174, 71%). Metabolic risk factors were more prevalent in the steatosis group. The mean UI-value in the total cohort was 0.90 (± 0.15). The HRQL (UI-value) was significantly lower in PLWH and steatosis in comparison to no steatosis (p = 0.013). The most strongly affected dimensions were mobility (p = 0.016) and pain/discomfort (p = 0.012) in the steatosis group, and the dimension anxiety/depression was equally impaired in both groups (p = 0.629). Unemployment (beta = -0.270, p = 0.025) and waist circumference (beta = -0.289, p = 0.017) remained independent predictors of a poor HRQL in the steatosis subgroup. In turn, age (beta = -0.168, p = 0.045), female sex (beta = -0.173, p = 0.030), BMI (beta = -0.214, p = 0.010) and arterial hypertension (beta = -0.194, p = 0.025) were independent predictors of a low HRQL in the subgroup without steatosis.
Conclusion: Hepatic steatosis and metabolic comorbidities negatively affect HRQL. Addressing these factors may improve patient reported and liver related outcomes in PLWH.
COVID-19 May Increase the Risk of Herpes Zoster in Adults ≥50 Years of Age
A. Stuendl (München, DE)
Several case reports have described shingles (herpes zoster; HZ) occurring shortly after COVID-19 diagnosis, possibly due to SARS-CoV-2-induced T-cell immune dysfunction. However, these case reports could not determine whether patients with COVID-19 have a higher risk of developing HZ. We therefore assessed this in a retrospective cohort study.
We compared the HZ incidence in individuals ≥50 years old with a COVID-19 diagnosis (as well as in those hospitalized with COVID-19) versus those without COVID-19. We used data from the US Truven MarketScan Commercial Claims and Encounters and Medicare Supplemental databases (3/2020-2/2021) and Optum Clinformatics Data Mart database (3-12/2020). Individuals with COVID-19 were exact-matched 1:4 to individuals without COVID-19 by age, sex, HZ risk factors and healthcare cost. Relative risks (RRs) were estimated by Poisson regression.
394,677 individuals with COVID-19 were matched to 1,577,346 individuals without COVID-19. Baseline characteristics and length of follow-up were similar in both cohorts. The observed HZ incidence per 1,000 person-years was 8.16 (95% confidence interval [CI]: 7.63-8.72) in the COVID-19 and 6.81 (6.57-7.05) in the non-COVID-19 cohort; the RR estimate was 1.15 (95%CI: 1.07-1.24; p=0.0003). The HZ risk was numerically higher until 183 days after COVID-19 diagnosis. The RR of HZ in individuals hospitalized with COVID-19 versus those without COVID-19 was 1.21 (1.03-1.41; p=0.02).
This study showed that individuals ≥50 years old with COVID-19 had a 15% higher risk of HZ than those without COVID-19, highlighting the importance of maintaining adult immunization against non-COVID-19 diseases during the pandemic.