TY  - JOUR
AB  - INTRODUCTION: A lot of research has been done, mainly on tuberculosis (TB), on the extent to which cellular immune protection as measured by interferon-γ release assays (IGRA) is age-dependent. In a previous study we showed that following an Omicron infection, adolescents with a hybrid immunity had a higher probability of having a reactive SARS-CoV-2-specific IGRA than children. Therefore, we examined in a large group of minors and adults whether age influences cellular immunity as measured by IGRA in TB and SARS-CoV-2. METHODS: Participants were recruited at 13 German study sites between September and December 2022. Cellular immunity was analyzed using SARS-CoV-2 and Tb-specific IGRA and humoral immunity against SARS-CoV-2 by measuring antibodies against spike (S) and nucleocapsid protein. Analysis was done depending on natural (convalescent, not vaccinated) or hybrid immunity (convalescent and vaccinated). RESULTS: Overall, 1401 adults and 392 minors were included. The amount of interferon-γ released by T cells, as well as the probability of a positive SARS-CoV-2 IGRA (OR 1.022) and a positive Tb IGRA (OR 1.047) were age dependent. Sensitivity of SARS-CoV-2 IGRA in natural immunity was lower in minors (0.45), especially in those less than 5 years (0.29) as compared to adults (0.66). CONCLUSION: The interferon-γ response to SARS-CoV-2 infections and/or vaccinations and to Tb infections as measured by IGRA is in quality and quantity dependent on age. The sensitivity of commercially available tests in young children seems to be suboptimal, limiting their use as a diagnostic or research tool in this age group.
AU  - Rothoeft, T.*
AU  - Hoffmann, A.T.*
AU  - Maier, C.*
AU  - Denz, R.*
AU  - Kobbe, R.*
AU  - Friedrichs, A.*
AU  - Behrens, G.M.N.*
AU  - Behrens, P.*
AU  - Berner, R.*
AU  - Caliebe, A.*
AU  - Denkinger, C.M.*
AU  - Giesbrecht, K.*
AU  - Hojenski, L.*
AU  - Hovardovska, O.*
AU  - Dopfer-Jablonka, A.*
AU  - Iatseniuk, O.*
AU  - Kaasch, A.J.*
AU  - Kraus, M.
AU  - Mitrov, L.*
AU  - Nauck, M.*
AU  - de Miranda, S.N.*
AU  - Scherer, M.*
AU  - Schmiedel, Y.*
AU  - Stahl, D.*
AU  - Timmesfeld, N.*
AU  - Toepfner, N.*
AU  - Vehreschild, J.*
AU  - Wohlgemuth, W.A.*
AU  - Petersmann, A.*
AU  - Vehreschild, M.J.G.T.*
AU  - Brinkmann, F.*
C1  - 75273
C2  - 57885
CY  - Tiergartenstrasse 17, D-69121 Heidelberg, Germany
TI  - Performance of whole blood interferon-γ release assays in SARS-CoV-2 and tuberculosis is age dependent.
JO  - Infection
PB  - Springer Heidelberg
PY  - 2025
SN  - 0300-8126
ER  - 

TY  - JOUR
AB  - BACKGROUND: A considerable number of patients who contracted SARS-CoV-2 are affected by persistent multi-systemic symptoms, referred to as Post-COVID Condition (PCC). Post-exertional malaise (PEM) has been recognized as one of the most frequent manifestations of PCC and is a diagnostic criterion of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Yet, its underlying pathomechanisms remain poorly elucidated. PURPOSE AND METHODS: In this review, we describe current evidence indicating that key pathophysiological features of PCC and ME/CFS are involved in physical activity-induced PEM. RESULTS: Upon physical activity, affected patients exhibit a reduced systemic oxygen extraction and oxidative phosphorylation capacity. Accumulating evidence suggests that these are mediated by dysfunctions in mitochondrial capacities and microcirculation that are maintained by latent immune activation, conjointly impairing peripheral bioenergetics. Aggravating deficits in tissue perfusion and oxygen utilization during activities cause exertional intolerance that are frequently accompanied by tachycardia, dyspnea, early cessation of activity and elicit downstream metabolic effects. The accumulation of molecules such as lactate, reactive oxygen species or prostaglandins might trigger local and systemic immune activation. Subsequent intensification of bioenergetic inflexibilities, muscular ionic disturbances and modulation of central nervous system functions can lead to an exacerbation of existing pathologies and symptoms.
AU  - Haunhorst, S.*
AU  - Dudziak, D.*
AU  - Scheibenbogen, C.*
AU  - Seifert, M.*
AU  - Sotzny, F.*
AU  - Finke, C.*
AU  - Behrends, U.
AU  - Aden, K.*
AU  - Schreiber, S.*
AU  - Brockmann, D.*
AU  - Burggraf, P.*
AU  - Bloch, W.*
AU  - Ellert, C.*
AU  - Ramoji, A.*
AU  - Popp, J.*
AU  - Reuken, P.*
AU  - Walter, M.*
AU  - Stallmach, A.*
AU  - Puta, C.*
C1  - 71637
C2  - 56326
CY  - Tiergartenstrasse 17, D-69121 Heidelberg, Germany
TI  - Towards an understanding of physical activity-induced post-exertional malaise: Insights into microvascular alterations and immunometabolic interactions in post-COVID condition and myalgic encephalomyelitis/chronic fatigue syndrome.
JO  - Infection
PB  - Springer Heidelberg
PY  - 2024
SN  - 0300-8126
ER  - 

TY  - JOUR
AB  - PURPOSE: The influence of new SARS-CoV-2 variants on the post-COVID-19 condition (PCC) remains unanswered. Therefore, we examined the prevalence and predictors of PCC-related symptoms in patients infected with the SARS-CoV-2 variants delta or omicron. METHODS: We compared prevalences and risk factors of acute and PCC-related symptoms three months after primary infection (3MFU) between delta- and omicron-infected patients from the Cross-Sectoral Platform of the German National Pandemic Cohort Network. Health-related quality of life (HrQoL) was determined by the EQ-5D-5L index score and trend groups were calculated to describe changes of HrQoL between different time points. RESULTS: We considered 758 patients for our analysis (delta: n = 341; omicron: n = 417). Compared with omicron patients, delta patients had a similar prevalence of PCC at the 3MFU (p = 0.354), whereby fatigue occurred most frequently (n = 256, 34%). HrQoL was comparable between the groups with the lowest EQ-5D-5L index score (0.75, 95% CI 0.73-0.78) at disease onset. While most patients (69%, n = 348) never showed a declined HrQoL, it deteriorated substantially in 37 patients (7%) from the acute phase to the 3MFU of which 27 were infected with omicron. CONCLUSION: With quality-controlled data from a multicenter cohort, we showed that PCC is an equally common challenge for patients infected with the SARS-CoV-2 variants delta and omicron at least for the German population. Developing the EQ-5D-5L index score trend groups showed that over two thirds of patients did not experience any restrictions in their HrQoL due to or after the SARS-CoV-2 infection at the 3MFU. CLINICAL TRAIL REGISTRATION: The cohort is registered at ClinicalTrials.gov since February 24, 2021 (Identifier: NCT04768998).
AU  - Hopff, S.M.*
AU  - Appel, K.S.*
AU  - Miljukov, O.*
AU  - Schneider, J.*
AU  - Addo, M.M.*
AU  - Bals, R.*
AU  - Bercker, S.*
AU  - Blaschke, S.*
AU  - Bröhl, I.*
AU  - Büchner, N.*
AU  - Dashti, H.S.*
AU  - Erber, J.*
AU  - Friedrichs, A.*
AU  - Geisler, R.*
AU  - Göpel, S.*
AU  - Hagen, M.*
AU  - Hanses, F.*
AU  - Jensen, B.O.*
AU  - Keul, M.*
AU  - Krawczyk, A.*
AU  - Lorenz-Depiereux, B.
AU  - Meybohm, P.*
AU  - Milovanovic, M.*
AU  - Mitrov, L.*
AU  - Nürnberger, C.*
AU  - Obst, W.*
AU  - Römmele, C.*
AU  - Schäfer, C.*
AU  - Scheer, C.E.*
AU  - Scherer, M.*
AU  - Schmidt, J.*
AU  - Seibel, K.*
AU  - Sikdar, S.*
AU  - Tebbe, J.J.*
AU  - Tepasse, P.R.*
AU  - Thelen, P.*
AU  - Vehreschild, M.J.G.T.*
AU  - Weismantel, C.*
AU  - Vehreschild, J.J.*
C1  - 70626
C2  - 55780
CY  - Tiergartenstrasse 17, D-69121 Heidelberg, Germany
TI  - Comparison of post-COVID-19 symptoms in patients infected with the SARS-CoV-2 variants delta and omicron-results of the Cross-Sectoral Platform of the German National Pandemic Cohort Network (NAPKON-SUEP).
JO  - Infection
PB  - Springer Heidelberg
PY  - 2024
SN  - 0300-8126
ER  - 

TY  - JOUR
AB  - Introduction: Following lockdown periods and restricting public health measures in response to the COVID-19 pandemic, respiratory tract infections (RTIs) rose significantly worldwide. This led to an increased burden on children’s hospitals compromising medical care of acutely and chronically ill children. We characterized changes in the epidemiological pattern of circulating respiratory viral infections. Methods: We assessed the number of patients with RTIs and the annual distribution of virus detections between 2019 and 2022 based on 4809 clinical samples (4131 patients) from a German pediatric tertiary care-center. We investigated the impact of lockdown periods on spectra of circulating respiratory viruses, pattern of coinfections, age, and seasonality of infections. Results: A fourfold increase in the number of respiratory virus detections was observed in 2022 vs 2019 with numbers doubling in 2022 (vs 2021). In 2022, seasonal patterns of circulating virus, particularly Adeno and seasonal Coronavirus were far less pronounced compared to previous years, in fact almost disappeared for Rhinoviruses.”. SARS-CoV-2, Parainfluenza- and human Metapneumovirus detections increased significantly in 2022 (2019 vs 2022, p < 0.01). Coinfections with multiple viruses occurred more frequently since 2021 compared to pre-pandemic years, especially in younger children (2019 vs 2022, p < 0.01). Conclusion: Compared to pre-pandemic years, we observed a dramatic increase in pediatric RTIs with an incrementing spectrum of viruses and a predominance in Rhino/Enterovirus infections – leading to a high rate of hospital admissions, particularly in conjunction with other viruses. This caused an acute shortage in medical care and may also be followed by an increase of virus-triggered secondary chronic respiratory diseases like asthma—rendering a burden on the health system.
AU  - Maison, N.
AU  - Omony, J.
AU  - Rinderknecht, S.*
AU  - Kolberg, L.*
AU  - Meyer-Bühn, M.*
AU  - von Mutius, E.
AU  - Hübner, J.*
AU  - von Both, U.*
C1  - 68341
C2  - 54763
CY  - Tiergartenstrasse 17, D-69121 Heidelberg, Germany
SP  - 209-218
TI  - Old foes following news ways?—Pandemic-related changes in the epidemiology of viral respiratory tract infections.
JO  - Infection
VL  - 52
IS  - 1
PB  - Springer Heidelberg
PY  - 2024
SN  - 0300-8126
ER  - 

TY  - JOUR
AB  - PURPOSE: This study assessed the clinical and immunological outcomes of SARS-CoV-2-infected patients with risk factors for severe disease depending on their immunological status. METHODS: In this retrospective study with single follow-up visit, clinical outcome and humoral immunity was monitored in SARS-CoV-2 infected patients at risk. The results were compared based on the patients' initial immunological status: unvaccinated (UV), patients who did not develop neutralizing antibodies after vaccination (vaccine non-responders, VNR), and patients who expressed neutralizing antibodies after vaccination (vaccine responders, VR). Patients who lacked neutralizing antibodies (VNR and UV) were treated with nMABs. RESULTS: In total, 113 patients at risk of severe COVID-19 consented to participate in the study. VR and UV were not admitted to the hospital. During the observation period, UVs had the highest rate of SARS-CoV-2 re-infections. Three of 41 VNRs (7.3%) were hospitalized due to severe COVID-19, with two of them having undergone iatrogenic B-cell depletion. The humoral immune response after infection was significantly lower in the VNR group than in the VR group in terms of anti-N, anti-receptor-binding domain (RBD), anti-S antibody titers, and anti-S antibody avidity. In a sub-analysis of VNR, B cell-deficient non-responders had significantly lower levels of anti-N antibodies and anti-S avidity after infection than other VNRs. CONCLUSION: VNR, particularly B-cell-depleted VNR, remained at risk of hospitalization due to COVID-19. In the VR group, however, no clinical complications or severe disease were observed, despite not receiving nMAbs. Tailoring the administration of nMABs according to patient vaccination and immunological status may be advisable.
AU  - Triebelhorn, J.*
AU  - Schneider, J.*
AU  - Spinner, C.D.*
AU  - Iakoubov, R.*
AU  - Voit, F.*
AU  - Wagner, L.*
AU  - Erber, J.*
AU  - Rothe, K.*
AU  - Berthele, A.*
AU  - Pernpeintner, V.*
AU  - Strauß, E.M.*
AU  - Renders, L.*
AU  - Willmann, A.
AU  - Minic, M.
AU  - Vogel, E.
AU  - Christa, C.
AU  - Hoffmann, D.
AU  - Protzer, U.
AU  - Jeske, S.
C1  - 69889
C2  - 55307
CY  - Tiergartenstrasse 17, D-69121 Heidelberg, Germany
TI  - Clinical and immunological outcomes of SARS-CoV-2-infected vaccine responders, vaccine non-responders, and unvaccinated patients evaluated for neutralizing monoclonal antibody treatment at a single German tertiary care center: A retrospective cohort study with prospective follow-up.
JO  - Infection
PB  - Springer Heidelberg
PY  - 2024
SN  - 0300-8126
ER  - 

TY  - JOUR
AB  - PURPOSE: A host-protein signature score, consisting of serum-concentrations of C-reactive protein, tumour necrosis factor-related apoptosis-inducing ligand, and interferon gamma-induced protein 10, was validated for distinguishing between bacterial and viral infections as an antimicrobial stewardship measure for routine clinical practice among adult patients in a German tertiary hospital. METHODS: This single-centre, explorative study prospectively assessed the host-protein signature score, comparing it with serum procalcitonin (PCT) in patients with blood stream infections (BSI) and evaluating its efficacy in patients with viral infections against the standard of care (SOC) to assess the need for antibiotics due to suspected bacterial super/coinfection. Manufacturer-specified threshold scores were used to differentiate viral (< 35) and bacterial (> 65) infections. RESULTS: Ninety-seven patients (BSI [n = 56]; viral infections [n = 41]) were included. The score (cut-off score > 65) tended to detect BSI with higher sensitivity than did PCT (cut-off > 0.5 ng/mL) (87.5% vs. 76.6%). Three patients (5.4%) with BSI had a score < 35. One patient with BSI did not receive antibiotic treatment following SOC prior to positive blood culture results. Among patients with viral infections, 29 (70.7%) had scores > 65, indicating bacterial superinfections. Additionally, 11 patients (26.8%) had scores < 35, indicating no bacterial superinfections. In total, the antibiotic treatment discrepancy in the viral group between the SOC and a host-protein signature score guided approach was 2/41 patients (4.9%). CONCLUSION: The score tended towards a higher sensitivity in detecting BSI than that with PCT. However, its impact on reducing antibiotic use in viral infections was minor compared with that of SOC.
AU  - Wagner, L.*
AU  - Schneider, H.*
AU  - Luppa, P.B.*
AU  - Schröder, K.*
AU  - Wantia, N.*
AU  - Querbach, C.*
AU  - Jeske, S.
AU  - Lahmer, T.*
AU  - Rothe, K.*
AU  - Dibos, M.*
AU  - Voit, F.*
AU  - Erber, J.*
AU  - Spinner, C.D.*
AU  - Schneider, J.*
AU  - Triebelhorn, J.*
C1  - 71647
C2  - 56331
CY  - Tiergartenstrasse 17, D-69121 Heidelberg, Germany
TI  - Evaluation of a host-protein signature score for differentiating between bacterial and viral infections: Real-life evidence from a German tertiary hospital.
JO  - Infection
PB  - Springer Heidelberg
PY  - 2024
SN  - 0300-8126
ER  - 

TY  - JOUR
AB  - OBJECTIVES: To determine the impact of the COVID-19 pandemic on the incidence rates of infection and islet autoimmunity in children at risk for type 1 diabetes. METHODS: 1050 children aged 4 to 7 months with an elevated genetic risk for type 1 diabetes were recruited from Germany, Poland, Sweden, Belgium and the UK. Reported infection episodes and islet autoantibody development were monitored until age 40 months from February 2018 to February 2023. RESULTS: The overall infection rate was 311 (95% Confidence Interval [CI], 304-318) per 100 person years. Infection rates differed by age, country, family history of type 1 diabetes, and period relative to the pandemic. Total infection rates were 321 per 100 person-years (95% CI 304-338) in the pre-pandemic period (until February 2020), 160 (95% CI 148-173) per 100 person-years in the first pandemic year (March 2020-February 2021; P < 0.001) and 337 (95% CI 315-363) per 100 person-years in subsequent years. Similar trends were observed for respiratory and gastrointestinal infections. Islet autoantibody incidence rates were 1.6 (95% CI 1.0-2.4) per 100 person-years in the pre-pandemic period, 1.2 (95% CI 0.8-1.9) per 100 person-years in the first pandemic year (P = 0.46), and 3.4 (95% CI 2.3-4.8) per 100 person-years in subsequent years (P = 0.005 vs. pre-pandemic year; P < 0.001 vs. first pandemic year). CONCLUSIONS: The COVID-19 pandemic was associated with significantly altered infection patterns. Islet autoantibody incidence rates increased two-fold when infection rates returned to pre-pandemic levels.
AU  - Zeller, I.
AU  - Weiss, A.
AU  - Arnolds, S.
AU  - Schütte-Borkovec,K.
AU  - Arabi, S.*
AU  - von dem Berge, T.*
AU  - Casteels, K.*
AU  - Hommel, A.*
AU  - Kordonouri, O.*
AU  - Larsson, H.E.*
AU  - Lundgren, M.*
AU  - Rochtus, A.*
AU  - Snape, M.D.*
AU  - Szypowka, A.*
AU  - Vatish, M.*
AU  - Winkler, C.
AU  - Bonifacio, E.
AU  - Ziegler, A.-G.
C1  - 70835
C2  - 55946
CY  - Tiergartenstrasse 17, D-69121 Heidelberg, Germany
TI  - Infection episodes and islet autoantibodies in children at increased risk for type 1 diabetes before and during the COVID-19 pandemic.
JO  - Infection
PB  - Springer Heidelberg
PY  - 2024
SN  - 0300-8126
ER  - 

TY  - JOUR
AB  - PURPOSE: Lung transplant recipients are at increased risk of severe disease following infection with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) due to high-dose immunosuppressive drugs and the lung is the main organ affected by Coronavirus disease 2019 (COVID-19). Several studies have confirmed increased SARS-CoV-2-related mortality and morbidity in patients living with lung allografts; however, detailed immunological studies of patients with SARS-CoV-2 infection in the early phase following transplantation remain scarce. METHODS: We investigated patients who were infected with SARS-CoV-2 in the early phase (18-103 days) after receiving double-lung allografts (n = 4, LuTx) in comparison to immunocompetent patients who had not received solid organ transplants (n = 88, noTx). We analyzed SARS-CoV-2-specific antibody responses against the SARS-CoV-2 spike and nucleocapsid proteins using enzyme-linked immunosorbent assays (ELISA), chemiluminescence immunoassays (CLIA), and immunoblot assays. T cell responses were investigated using Elispot assays. RESULTS: One LuTx patient suffered from persistent infection with fatal outcome 122 days post-infection despite multiple interventions including remdesivir, convalescent plasma, and the monoclonal antibody bamlanivimab. Two patients experienced clinically mild disease with prolonged viral shedding (47 and 79 days), and one patient remained asymptomatic. Antibody and T cell responses were significantly reduced or undetectable in all LuTx patients compared to noTx patients. CONCLUSION: Patients in the early phase following lung allograft transplantation are vulnerable to infection with SARS-CoV-2 due to impaired immune responses. This patient population should be vaccinated before LuTx, protected from infection post-LuTx, and in case of infection treated generously with currently available interventions.
AU  - Glueck, O.M.*
AU  - Liang, X.*
AU  - Badell, I.*
AU  - Wratil, P.R.*
AU  - Graf, A.*
AU  - Krebs, S.*
AU  - Blum, H.*
AU  - Hellmuth, J.C.*
AU  - Scherer, C.*
AU  - Hollaus, A.
AU  - Spaeth, P.M.*
AU  - Karakoc, B.*
AU  - Fuchs, T.*
AU  - Zimmermann, J.*
AU  - Kauke, T.*
AU  - Moosmann, A.
AU  - Keppler, O.T.*
AU  - Schneider, C.*
AU  - Muenchhoff, M.*
C1  - 68727
C2  - 54936
TI  - Impaired immune responses and prolonged viral replication in lung allograft recipients infected with SARS-CoV-2 in the early phase after transplantation.
JO  - Infection
PY  - 2023
SN  - 0300-8126
ER  - 

TY  - JOUR
AB  - PURPOSE: We aimed to assess symptoms in patients after SARS-CoV-2 infection and to identify factors predicting prolonged time to symptom-free. METHODS: COVIDOM/NAPKON-POP is a population-based prospective cohort of adults whose first on-site visits were scheduled ≥ 6 months after a positive SARS-CoV-2 PCR test. Retrospective data including self-reported symptoms and time to symptom-free were collected during the survey before a site visit. In the survival analyses, being symptom-free served as the event and time to be symptom-free as the time variable. Data were visualized with Kaplan-Meier curves, differences were tested with log-rank tests. A stratified Cox proportional hazard model was used to estimate adjusted hazard ratios (aHRs) of predictors, with aHR < 1 indicating a longer time to symptom-free. RESULTS: Of 1175 symptomatic participants included in the present analysis, 636 (54.1%) reported persistent symptoms after 280 days (SD 68) post infection. 25% of participants were free from symptoms after 18 days [quartiles: 14, 21]. Factors associated with prolonged time to symptom-free were age 49-59 years compared to < 49 years (aHR 0.70, 95% CI 0.56-0.87), female sex (aHR 0.78, 95% CI 0.65-0.93), lower educational level (aHR 0.77, 95% CI 0.64-0.93), living with a partner (aHR 0.81, 95% CI 0.66-0.99), low resilience (aHR 0.65, 95% CI 0.47-0.90), steroid treatment (aHR 0.22, 95% CI 0.05-0.90) and no medication (aHR 0.74, 95% CI 0.62-0.89) during acute infection. CONCLUSION: In the studied population, COVID-19 symptoms had resolved in one-quarter of participants within 18 days, and in 34.5% within 28 days. Over half of the participants reported COVID-19-related symptoms 9 months after infection. Symptom persistence was predominantly determined by participant's characteristics that are difficult to modify.
AU  - Shi, Y.*
AU  - Strobl, R.*
AU  - Apfelbacher, C.*
AU  - Bahmer, T.*
AU  - Geißler, R.*
AU  - Heuschmann, P.*
AU  - Horn, A.*
AU  - Hoven, H.*
AU  - Keil, T.*
AU  - Krawczak, M.*
AU  - Krist, L.*
AU  - Lemhöfer, C.*
AU  - Lieb, W.*
AU  - Lorenz-Depiereux, B.
AU  - Mikolajczyk, R.*
AU  - Montellano, F.A.*
AU  - Reese, J.P.*
AU  - Schreiber, S.*
AU  - Skoetz, N.*
AU  - Störk, S.*
AU  - Vehreschild, J.J.*
AU  - Witzenrath, M.*
AU  - Grill, E.*
C1  - 67890
C2  - 54368
CY  - Tiergartenstrasse 17, D-69121 Heidelberg, Germany
SP  - 1679-1694
TI  - Persistent symptoms and risk factors predicting prolonged time to symptom-free after SARS‑CoV‑2 infection: An analysis of the baseline examination of the German COVIDOM/NAPKON-POP cohort.
JO  - Infection
VL  - 51
IS  - 6
PB  - Springer Heidelberg
PY  - 2023
SN  - 0300-8126
ER  - 

TY  - JOUR
AB  - BACKGROUND: The severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) pandemic causes a high burden of acute and long-term morbidity and mortality worldwide despite global efforts in containment, prophylaxis, and therapy. With unprecedented speed, the global scientific community has generated pivotal insights into the pathogen and the host response evoked by the infection. However, deeper characterization of the pathophysiology and pathology remains a high priority to reduce morbidity and mortality of coronavirus disease 2019 (COVID-19). METHODS: NAPKON-HAP is a multi-centered prospective observational study with a long-term follow-up phase of up to 36 months post-SARS-CoV-2 infection. It constitutes a central platform for harmonized data and biospecimen for interdisciplinary characterization of acute SARS-CoV-2 infection and long-term outcomes of diverging disease severities of hospitalized patients. RESULTS: Primary outcome measures include clinical scores and quality of life assessment captured during hospitalization and at outpatient follow-up visits to assess acute and chronic morbidity. Secondary measures include results of biomolecular and immunological investigations and assessment of organ-specific involvement during and post-COVID-19 infection. NAPKON-HAP constitutes a national platform to provide accessibility and usability of the comprehensive data and biospecimen collection to global research. CONCLUSION: NAPKON-HAP establishes a platform with standardized high-resolution data and biospecimen collection of hospitalized COVID-19 patients of different disease severities in Germany. With this study, we will add significant scientific insights and provide high-quality data to aid researchers to investigate COVID-19 pathophysiology, pathology, and chronic morbidity.
AU  - Steinbeis, F.*
AU  - Thibeault, C.*
AU  - Steinbrecher, S.*
AU  - Ahlgrimm, Y.*
AU  - Haack, I.A.*
AU  - August, D.*
AU  - Balzuweit, B.*
AU  - Bellinghausen, C.*
AU  - Berger, S.*
AU  - Chaplinskaya-Sobol, I.*
AU  - Cornely, O.*
AU  - Doeblin, P.*
AU  - Endres, M.*
AU  - Fink, C.*
AU  - Finke, C.*
AU  - Frank, S.*
AU  - Hans, S.*
AU  - Hartung, T.*
AU  - Hellmuth, J.C.*
AU  - Herold, S.*
AU  - Heuschmann, P.*
AU  - Heyckendorf, J.*
AU  - Heyder, R.*
AU  - Hippenstiel, S.*
AU  - Hoffmann, W.*
AU  - Kelle, S.U.*
AU  - Knape, P.*
AU  - Koehler, P.*
AU  - Kretzler, L.*
AU  - Leistner, D.M.*
AU  - Lienau, J.*
AU  - Lorbeer, R.*
AU  - Lorenz-Depiereux, B.
AU  - Lüttke, C.D.*
AU  - Mai, K.*
AU  - Merle, U.*
AU  - Meyer-Arndt, L.A.*
AU  - Miljukov, O.*
AU  - Muenchhoff, M.*
AU  - Müller-Plathe, M.*
AU  - Neuhann, J.*
AU  - Neuhauser, H.*
AU  - Nieters, A.*
AU  - Otte, C.*
AU  - Pape, D.*
AU  - Pinto, R.M.*
AU  - Pley, C.*
AU  - Pudszuhn, A.*
AU  - Reuken, P.*
AU  - Rieg, S.*
AU  - Ritter, P.*
AU  - Rohde, G.*
AU  - Rönnefarth, M.*
AU  - Ruzicka, M.*
AU  - Schaller, J.*
AU  - Schmidt, A.*
AU  - Schmidt, S.*
AU  - Schwachmeyer, V.*
AU  - Schwanitz, G.*
AU  - Seeger, W.*
AU  - Stahl, D.*
AU  - Stobäus, N.*
AU  - Stubbe, H.C.*
AU  - Suttorp, N.*
AU  - Temmesfeld, B.*
AU  - Thun, S.*
AU  - Triller, P.*
AU  - Trinkmann, F.*
AU  - Vadász, I.*
AU  - Valentin, H.*
AU  - Vehreschild, M.*
AU  - von Kalle, C.*
AU  - von Lilienfeld-Toal, M.*
AU  - Weber, J.*
AU  - Welte, T.*
AU  - Wildberg, C.*
AU  - Wizimirski, R.*
AU  - Zvork, S.*
AU  - Sander, L.E.*
AU  - Vehreschild, J.*
AU  - Zöller, T.*
AU  - Kurth, F.*
AU  - Witzenrath, M.*
C1  - 68118
C2  - 54596
CY  - Tiergartenstrasse 17, D-69121 Heidelberg, Germany
TI  - Analysis of acute COVID-19 including chronic morbidity: Protocol for the deep phenotyping National Pandemic Cohort Network in Germany (NAPKON-HAP).
JO  - Infection
PB  - Springer Heidelberg
PY  - 2023
SN  - 0300-8126
ER  - 

TY  - JOUR
AB  - PURPOSE: Over the course of COVID-19 pandemic, evidence has accumulated that SARS-CoV-2 infections may affect multiple organs and have serious clinical sequelae, but on-site clinical examinations with non-hospitalized samples are rare. We, therefore, aimed to systematically assess the long-term health status of samples of hospitalized and non-hospitalized SARS-CoV-2 infected individuals from three regions in Germany. METHODS: The present paper describes the COVIDOM-study within the population-based cohort platform (POP) which has been established under the auspices of the NAPKON infrastructure (German National Pandemic Cohort Network) of the national Network University Medicine (NUM). Comprehensive health assessments among SARS-CoV-2 infected individuals are conducted at least 6 months after the acute infection at the study sites Kiel, Würzburg and Berlin. Potential participants were identified and contacted via the local public health authorities, irrespective of the severity of the initial infection. A harmonized examination protocol has been implemented, consisting of detailed assessments of medical history, physical examinations, and the collection of multiple biosamples (e.g., serum, plasma, saliva, urine) for future analyses. In addition, patient-reported perception of the impact of local pandemic-related measures and infection on quality-of-life are obtained. RESULTS: As of July 2021, in total 6813 individuals infected in 2020 have been invited into the COVIDOM-study. Of these, about 36% wished to participate and 1295 have already been examined at least once. CONCLUSION: NAPKON-POP COVIDOM-study complements other Long COVID studies assessing the long-term consequences of an infection with SARS-CoV-2 by providing detailed health data of population-based samples, including individuals with various degrees of disease severity. TRIAL REGISTRATION: Registered at the German registry for clinical studies (DRKS00023742).
AU  - Horn, A.P.*
AU  - Krist, L.*
AU  - Lieb, W.*
AU  - Montellano, F.A.*
AU  - Kohls, M.*
AU  - Haas, K.*
AU  - Gelbrich, G.*
AU  - Bolay-Gehrig, S.J.*
AU  - Morbach, C.*
AU  - Reese, J.P.*
AU  - Störk, S.*
AU  - Fricke, J.*
AU  - Zöller, T.*
AU  - Schmidt, S.*
AU  - Triller, P.*
AU  - Kretzler, L.*
AU  - Rönnefarth, M.*
AU  - von Kalle, C.*
AU  - Willich, S.N.*
AU  - Kurth, F.*
AU  - Steinbeis, F.*
AU  - Witzenrath, M.*
AU  - Bahmer, T.*
AU  - Hermes, A.*
AU  - Krawczak, M.*
AU  - Reinke, L.*
AU  - Maetzler, C.*
AU  - Franzenburg, J.*
AU  - Enderle, J.*
AU  - Flinspach, A.*
AU  - Vehreschild, J.*
AU  - Schons, M.*
AU  - Illig, T.*
AU  - Anton, G.
AU  - Ungethüm, K.*
AU  - Finkenberg, B.C.*
AU  - Gehrig, M.T.*
AU  - Savaskan, N.*
AU  - Heuschmann, P.U.*
AU  - Keil, T.*
AU  - Schreiber, S.*
C1  - 63277
C2  - 51450
CY  - Tiergartenstrasse 17, D-69121 Heidelberg, Germany
SP  - 1277-1287
TI  - Long-term health sequelae and quality of life at least 6 months after infection with SARS-CoV-2: Design and rationale of the COVIDOM-study as part of the NAPKON population-based cohort platform (POP).
JO  - Infection
VL  - 49
IS  - 6
PB  - Springer Heidelberg
PY  - 2022
SN  - 0300-8126
ER  - 

TY  - JOUR
AB  - Background: During COVID-19-related public health non-pharmaceutical prevention measures, such as social distancing, lockdown periods and use of face masks, a decrease in viral respiratory and gastroenterological infections was observed worldwide. Following discontinuation of preventative measures, a potential increase of respective infections outside of their usual seasons was a matter of concern. Method: We aimed to illustrate annual distribution of confirmed viral infections between 2017 and 2021 based on 32,506 clinical samples in a German pediatric tertiary care center and to explore the impact of the COVID-19 pandemic on the epidemiology of these infections in children. Results: While a decrease in overall viral infections was observed during the first and second lockdown period, an extraordinary increase in the number of viral respiratory infections, predominantly caused by human Rhino-/Enterovirus and respiratory syncytial virus (RSV), was observed after relaxation of preventive measures. Notably, Rhino-/Enterovirus infections increased 4-fold (2020 vs. 2019) and 16-fold (2021 vs. 2019). The occurrence of RSV was observed beginning from June to August 2021 and reached an all-time record with a 25- to 50-fold increase in numbers in September and October 2021 in relation to previous pre-pandemic years (2017–2019). In contrast, for non-respiratory viruses (i.e. Rota-/Norovirus), the effect on respective seasonal patterns was only minimal compared to previous years. Conclusion: The observed increase in respiratory infections in children is worrying and is already causing hospitals to become overburdened. Enhanced vigilance will be key to face clinical challenges due to these epidemiological changes in viral disease patterns in the months to come.
AU  - Maison, N.
AU  - Peck, A.*
AU  - Illi, S.
AU  - Meyer-Buehn, M.*
AU  - von Mutius, E.
AU  - Hübner, J.*
AU  - von Both, U.*
C1  - 64199
C2  - 52100
CY  - Tiergartenstrasse 17, D-69121 Heidelberg, Germany
SP  - 519-524
TI  - The rising of old foes: Impact of lockdown periods on “non-SARS-CoV-2” viral respiratory and gastrointestinal infections.
JO  - Infection
VL  - 50
IS  - 2
PB  - Springer Heidelberg
PY  - 2022
SN  - 0300-8126
ER  - 

TY  - JOUR
AB  - Purpose Knowledge regarding patients' clinical condition at severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection is sparse. Data in the international, multicenter Lean European Open Survey on SARS-CoV-2-Infected Patients (LEOSS) cohort study may enhance the understanding of COVID-19. Methods Sociodemographic and clinical characteristics of SARS-CoV-2-infected patients, enrolled in the LEOSS cohort study between March 16, 2020, and May 14, 2020, were analyzed. Associations between baseline characteristics and clinical stages at diagnosis (uncomplicated vs. complicated) were assessed using logistic regression models. Results We included 2155 patients, 59.7% (1,287/2,155) were male; the most common age category was 66-85 years (39.6%; 500/2,155). The primary COVID-19 diagnosis was made in 35.0% (755/2,155) during complicated clinical stages. A significant univariate association between age; sex; body mass index; smoking; diabetes; cardiovascular, pulmonary, neurological, and kidney diseases; ACE inhibitor therapy; statin intake and an increased risk for complicated clinical stages of COVID-19 at diagnosis was found. Multivariable analysis revealed that advanced age [46-65 years: adjusted odds ratio (aOR): 1.73, 95% CI 1.25-2.42,p = 0.001; 66-85 years: aOR 1.93, 95% CI 1.36-2.74,p < 0.001; > 85 years: aOR 2.38, 95% CI 1.49-3.81,p < 0.001 vs. individuals aged 26-45 years], male sex (aOR 1.23, 95% CI 1.01-1.50,p = 0.040), cardiovascular disease (aOR 1.37, 95% CI 1.09-1.72,p = 0.007), and diabetes (aOR 1.33, 95% CI 1.04-1.69,p = 0.023) were associated with complicated stages of COVID-19 at diagnosis. Conclusion The LEOSS cohort identified age, cardiovascular disease, diabetes and male sex as risk factors for complicated disease stages at SARS-CoV-2 diagnosis, thus confirming previous data. Further data regarding outcomes of the natural course of COVID-19 and the influence of treatment are required.
AU  - Jakob, C.E.M.*
AU  - Borgmann, S.*
AU  - Duygu, F.*
AU  - Behrends, U.
AU  - Hower, M.*
AU  - Merle, U.*
AU  - Friedrichs, A.*
AU  - Tometten, L.*
AU  - Hanses, F.*
AU  - Jung, N.*
AU  - Rieg, S.*
AU  - Wille, K.*
AU  - Grüner, B.*
AU  - Klinker, H.*
AU  - Gersbacher-Runge, N.*
AU  - Hellwig, K.*
AU  - Eberwein, L.*
AU  - Dolff, S.*
AU  - Rauschning, D.*
AU  - von Bergwelt-Baildon, M.*
AU  - Lanznaster, J.*
AU  - Strauß, R.*
AU  - Trauth, J.*
AU  - de With, K.*
AU  - Ruethrich, M.*
AU  - Lueck, C.*
AU  - Nattermann, J.*
AU  - Tscharntke, L.*
AU  - Pilgram, L.*
AU  - Fuhrmann, S.*
AU  - Classen, A.*
AU  - Stecher, M.*
AU  - Schons, M.*
AU  - Spinner, C.*
AU  - Vehreschild, J.J.*
C1  - 60256
C2  - 49266
CY  - Tiergartenstrasse 17, D-69121 Heidelberg, Germany
SP  - 63–73
TI  - First results of the "Lean European Open Survey on SARS-CoV-2-Infected Patients (LEOSS)".
JO  - Infection
VL  - 49
PB  - Springer Heidelberg
PY  - 2021
SN  - 0300-8126
ER  - 

TY  - JOUR
AB  - Objective: Evaluation of pulmonary function impairment after COVID-19 in persistently symptomatic and asymptomatic patients of all disease severities and characterisation of risk factors. Methods: Patients with confirmed SARS-CoV-2 infection underwent prospective follow-up with pulmonary function testing and blood gas analysis during steady-state cycle exercise 4 months after acute illness. Pulmonary function impairment (PFI) was defined as reduction below 80% predicted of DLCOcSB, TLC, FVC, or FEV1. Clinical data were analyzed to identify risk factors for impaired pulmonary function. Results: 76 patients were included, hereof 35 outpatients with mild disease and 41 patients hospitalized due to COVID-19. Sixteen patients had critical disease requiring mechanical ventilation, 25 patients had moderate–severe disease. After 4 months, 44 patients reported persisting respiratory symptoms. Significant PFI was prevalent in 40 patients (52.6%) occurring among all disease severities. The most common cause for PFI was reduced DLCOcSB (n = 39, 51.3%), followed by reduced TLC and FVC. The severity of PFI was significantly associated with mechanical ventilation (p < 0.001). Further risk factors for DLCO impairment were COPD (p < 0.001), SARS-CoV-2 antibody-Titer (p = 0.014) and in hospitalized patients CT score. A decrease of paO2 > 3 mmHg during cycle exercise occurred in 1/5 of patients after mild disease course. Conclusion: We characterized pulmonary function impairment in asymptomatic and persistently symptomatic patients of different severity groups of COVID-19 and identified further risk factors associated with persistently decreased pulmonary function. Remarkably, gas exchange abnormalities were revealed upon cycle exercise in some patients with mild disease courses and no preexisting pulmonary condition.
AU  - Munker, D.
AU  - Veit, T.
AU  - Barton, J.
AU  - Mertsch, P.
AU  - Mümmler, C.
AU  - Osterman, A.*
AU  - Khatamzas, E.*
AU  - Barnikel, M.
AU  - Hellmuth, J.C.*
AU  - Münchhoff, M.*
AU  - Walter, J.
AU  - Ghiani, A.*
AU  - Munker, S.*
AU  - Dinkel, J.*
AU  - Behr, J.
AU  - Kneidinger, N.
AU  - Milger, K.
C1  - 62710
C2  - 50979
CY  - Tiergartenstrasse 17, D-69121 Heidelberg, Germany
TI  - Pulmonary function impairment of asymptomatic and persistently symptomatic patients 4 months after COVID-19 according to disease severity.
JO  - Infection
PB  - Springer Heidelberg
PY  - 2021
SN  - 0300-8126
ER  - 

TY  - JOUR
AB  - PURPOSE: To evaluate the diagnostic reliability and practicability of self-collected oropharyngeal swab samples for the detection of SARS-CoV-2 infection as self-sampling could enable broader testing availability and reduce both personal protective equipment and potential exposure. METHODS: Hospitalized SARS-CoV-2-infected patients were asked to collect two oropharyngeal swabs (SC-OPS1/2), and an additional oropharyngeal swab was collected by a health care professional (HCP-OPS). SARS-CoV-2 PCR testing for samples from 58 participants was performed, with a 48-h delay in half of the self-collected samples (SC-OPS2). The sensitivity, probability of concordance, and interrater reliability were calculated. Univariate and multivariate analyses were performed to assess predictive factors. Practicability was evaluated through a questionnaire. RESULTS: The test sensitivity for HCP-OPS, SC-OPS1, and SC-OPS2 was 88%, 78%, and 77%, respectively. Combining both SC-OPS results increased the estimated sensitivity to 88%. The concordance probability between HCP-OPS and SC-OPS1 was 77.6% and 82.5% between SC-OPS1 and SC-OPS2, respectively. Of the participants, 69% affirmed performing future self-sampling at home, and 34% preferred self-sampling over HCP-guided testing. Participants with both positive HCP-OPS1 and SC-OPS1 indicating no challenges during self-sampling had more differences in viral load levels between HCP-OPS1 and SC-OPS1 than those who indicated challenges. Increasing disease duration and the presence of anti-SARS-CoV-2-IgG correlated with negative test results in self-collected samples of previously confirmed SARS-CoV-2 positive individuals. CONCLUSION: Oropharyngeal self-sampling is an applicable testing approach for SARS-CoV-2 diagnostics. Self-sampling tends to be more effective in early versus late infection and symptom onset, and the collection of two distinct samples is recommended to maintain high test sensitivity.
AU  - Würstle, S.*
AU  - Spinner, C.D.*
AU  - Voit, F.*
AU  - Hoffmann, D.
AU  - Hering, S.
AU  - Weidlich, S.*
AU  - Schneider, J.*
AU  - Zink, A.*
AU  - Treiber, M.*
AU  - Iakoubov, R.*
AU  - Schmid, R.M.*
AU  - Protzer, U.
AU  - Erber, J.*
C1  - 62043
C2  - 50564
CY  - Tiergartenstrasse 17, D-69121 Heidelberg, Germany
SP  - 927-934
TI  - Self-sampling versus health care professional-guided swab collection for SARS-CoV-2 testing.
JO  - Infection
VL  - 49
IS  - 5
PB  - Springer Heidelberg
PY  - 2021
SN  - 0300-8126
ER  - 

TY  - JOUR
AB  - PURPOSE: Inadequate use of antibiotics can lead to problems such as resistance. Overuse is especially a problem for children, since they are more affected by acute (often virus-caused) infections. While the problem has been addressed internationally over the past several years, regional variations in prescriptions are striking. Therefore, the present study aims to analyze regional variations in antibiotic prescription on a district level in Germany and tries to identify reasons for those variations through adding possible influencing factors to the analysis on individual and district levels. METHODS: We analyzed 1.2 million children insured in a German health insurance fund. Antibiotic prescriptions were quantified in 2010 and reasons for prescriptions were analyzed in multilevel regressions based on the district of residence, regional deprivation, and age and sex of the child. RESULTS: Thirty-six percent of all children aged 0-17 years received an antibiotic prescription in 2010. In the south, prevalences are generally lower, and also to the very north. The highest prevalences are found in the close-to-border districts in the west, as well as in a band throughout the middle of Germany, in rather low population density areas. Regional variation in the prevalence range from 19 to 53 % between districts. Regional deprivation can explain part of this variation. CONCLUSIONS: Including area deprivation measures helped identify an influence of especially regional income and occupational deprivation on antibiotic prescriptions for children. Regional analysis such as this can help identify specific regions and groups of persons to address information programs on the risks of preventable antibiotic consumption and alternative treatment methods.
AU  - Koller, D.*
AU  - Hoffmann, F.*
AU  - Maier, W.
AU  - Tholen, K.*
AU  - Windt, R.*
AU  - Glaeske, G.*
C1  - 8337
C2  - 29274
SP  - 121-127
TI  - Variation in antibiotic prescriptions: Is area deprivation an explanation? Analysis of 1.2 million children in Germany.
JO  - Infection
VL  - 41
IS  - 1
PB  - Springer
PY  - 2013
SN  - 0300-8126
ER  - 

TY  - JOUR
AB  - 576 Serumproben von 139 HIV-infizierten Patienten wurden auf die Prävalenz von HIV-Antigen und die Titer der anti-env, anti-core und neutralisierenden Antikörper untersucht. Die Ergebnisse wurden mit den klinischen und immunologischen Stadien der Patienten korreliert. In fast allen Seren wurden Antikörper gegen env-Proteine und in zwei Drittel der Seren Antikörper gegen core-Proteine nachgewiesen. Die mittleren Antikörpertiter, insbesondere der anti-core Antikörper, fielen mit dem Auftreten klinischer Symptome ab. Nur 16% der Seren waren positiv für p24-Antigen. Der Nachweis von HIV-Antigen war meist assoziiert mit dem Fehlen von anti-core Antikörpern. Env-spezifische neutralisierende Antikörper wurden in allen im LC5-Test untersuchten Seren nachgewiesen, wobei Seren von WR 4-Patienten die höchsten Titer zeigten. Um als serologischer Marker geeignet zu sein, sollte ein Parameter einerseits in der überwiegenden Mehrzahl der untersuchten Proben Reaktivität und andererseits eine breite Streuung der Titerwerte zeigen. Keiner der hier untersuchten Parameter erfüllte diese Bedingungen. Deshalb beschreiben wir hier die Suche nach weiteren serologisch-immunologischen Markern, wie z.B. den Antikörpern gegen die regulatorischen HIV-Proteine.
AU  - Kleinschmidt, A.M.*
AU  - Matuschke, A.*
AU  - Goebel -, F.D.*
AU  - Erfle, V.F.
AU  - Hehlmann., R.*
C1  - 40837
C2  - 13103
SP  - S89-S92
TI  - Serological markers as prognostic criteria for the course of HIV infection.
JO  - Infection
VL  - 19
IS  - 2 Supplement
PY  - 1991
SN  - 0300-8126
ER  -