Impact of COVID-19 related alterations in circulating respiratory viruses on children and adult patients with recurrent wheeze and asthma

Introduction: The epidemiology of respiratory infections changed fundamentally during COVID-19 pandemic. While during lockdown periods numbers of respiratory infection were low, an increase of respiratory syncytial virus and rhinovirus infections was reported outside the natural season. Viral infections being the main trigger for asthma and wheeze episodes in children, we aimed to investigate the impact of this observation on children and adults. Method(s): Within the ALL Age Asthma Cohort (ALLIANCE), an observational, longitudinal multicenter asthma study, we assessed data regarding disease control, use of medication and etiology of exacerbations at three time points, during (pilot: Feb-Aug 2020: n= 280, phase 1: Oct-Apr 2020/21: n= 412) and after lockdown periods (phase 2: JunOct 2021: n= 327). Result(s): We observed high proportions of improvement in disease burden in preschool children (age 0-5.9 years) during lockdown periods in the pilot-phase (35%) and in phase 1 (32%). While after easing of hygiene measures none of the preschool children reported improvement (phase 1/phase 2;p = 0.02), 29% showed worsening of their condition (pilot/phase 2, p = 0.01) associated with viral infections and higher need for medication. Children aged 6-18 years showed a stable course over all phases. In contrast, adults reported worsening of their asthma (pilot, 19%, phase 1, 29%), but no significant change in phase 2 (23%). Conclusion(s): COVID-19 related measures caused a reduction and re-emerge of respiratory virus infections, which influenced the course of disease in preschool children with recurrent wheeze, but not in older children and adults with asthma.

Impact of COVID-19 related alterations in circulating respiratory viruses on children and adult patients with recurrent wheeze and asthma

Introduction During COVID-19 pandemic, the epidemiology of respiratory infections changed fundamentally. During lockdown periods rates of respiratory infection were low. An increase of respiratory syncytial virus and rhinovirus infections was reported after easing of hygiene measures compared to lockdown and pre-pandemic periods. We investigated the impact of this observation on children and adults with wheeze and asthma. Methods Within the ALL Age Asthma Cohort (ALLIANCE), we conducted questionnaires at three time points, during (Pilot: Feb-Aug 2020: n= 279, Phase 1: Oct-Apr 2020/21: n= 412) and after lockdown periods (Phase 2 Jun-Oct 2021: n= 327). Data on disease control (based on personal assessment and adapted GINA control status), use of medication and etiology of exacerbations were analyzed. Results Preschool children (age 0-5.9 years) showed a noticeable high improvement of 35% (Pilot) and 32% (Phase 1) in disease burden measured by specific symptoms and general personal assessment during lockdown periods. In contrast after easing of hygiene measures none of the preschoolers reported improvement compared to the beginning of the pandemic and lockdown phases (Pilot/ Phase 2;p= 0,0003;Phase 1/Phase 2;p = 0.004), but 29% showed worsening of their condition (Pilot/Phase 2, p = 0.02), associated with viral infections and higher need for medication. Children aged 6- 18 years had a stable asthma course over all phases. Adults reported higher proportion of worsening of their asthma in Phase 1 (30%) in comparison to the Pilot (19%), (p = 0.02), but not in Phase 2 (22%) compared to the Pilot (p= 0.39) or Phase 1 (p= 0.14). Conclusion COVID-19 related measures caused a reduction and re-emergence of respiratory virus infections, which influenced the course of disease in preschool children with recurrent wheeze, but not in older children and adults with asthma.

Prevalence of SARS-CoV-2 antibodies in hospital employees, Central Germany

Objectives Unidentified SARS-CoV-2 infections among hospital staff can become a major burden for healthcare systems worldwide. We hypothesized that the number of previous SARS-CoV-2 infections among hospital employees is substantially higher than known on the basis of direct testing strategies. A serological study was thus performed among staff of Marburg University Hospital, Germany, in May and June 2020. Methods Anti-SARS-CoV-2 antibody titers were measured by spike protein (S1)-specific IgG ELISA (Euroimmun) and by nucleoprotein-(NCP) specific total antibody CLIA (Roche). Selected sera were analyzed by SARS-CoV-2 neutralization test. Participants provided questionnaires regarding occupational, medical, and clinical items. Data for 3,623 individuals (74.7% of all employees) were collected. Results Individuals reactive to both S1 and NCP were defined as seropositive;all of those were confirmed by neutralization test (n=13). Eighty-nine samples were reactive in only one assay, and 3,521 were seronegative. The seroprevalence among hospital employees at Marburg University Hospital was 0.36% (13/3,623). Only five of the 13 seropositive employees had reported a positive SARS-CoV-2 RT-PCR test result. Conclusions Usage of a single S1-specific assay highly overestimated seroprevalence. The data provided no evidence for an increased risk for a SARS-CoV-2 infection for staff involved in patient care compared to staff not involved in patient care.

Quantitative pan-immunoglobulin titers against the receptor binding domain of the SARS-CoV-2 spike protein following infection with SARS-CoV-2

Aim: We aimed to determine the distribution of WHO-standardized quantitative measurements of pan-immunoglobulin titers against the receptor binding domain of the SARS-CoV-2 spike protein following SARSCoV- 2 infection. Design & Methods: In a retrospective analysis we analyzed anonymized routine data of patient samples with SARS-CoV-2 infection, as evidenced with a pan-immunoglobulin assay directed against nucleocapsid-antigen measured with an electrochemiluminescence immunoassay (ECLIA;Roche Diagnostics, Switzerland). Pan-immunoglobulin titers of antibodies directed against the receptor binding domain of the SARS-CoV-2 spike protein were measured with the same technology. Results are given as binding antibody units (BAU) per mL. Cut-off for positivity is >0.8 BAU/mL Results: A total of 1436 samples originating from patients (635 males;801 females) aged 52 (median, interquartile range, IQR, [38,64]) years were included. There was no correlation between age and antibody titers Females (111, IQR [27,>257] BAU/mL) had significantly lower median antibody titers than males (147, IQR [36,>257] BAU/mL;p = 0.03) The antibody levels at the 2.5, 5, 10, 25, 68th percentiles were 1,3,6,27 and >257 BAU/ml, in females. The antibody levels at the 2.5, 5, 10, 25 62nd percentiles were 0.4, 2, 9, 36, and >257 BAU/ml in males Conclusions: Among patients with evidence of past SARS-CoV-2 infection one third exhibits antibody titers above the upper quantification limit (i.e. 257 BAU/mL). Fifteen percent of female and 12% of male patients have antibody titers of 10 BAU/mL or lower.

Assessment of SARS-CoV-2 rapid antigen tests

Point-of-care antigen tests (PoC-AgTs) for the rapid detection of SARS-CoV-2 infection enable screening of additional populations with less effort, independent of laboratories and at a low cost. PoC-AgTs have therefore been included in national testing strategies with additional quality requirements to address limitations in specificity and sensitivity. Information given in the package inserts of the test providers should enable the user to evaluate the performance of a PoC-AgT in advance. The quality of this information has been independently assessed since the Corona Test Ordinance came into force in Germany in October 2020. The completeness of analytical and diagnostic performance specifications was assessed for all package inserts publicly available via the Paul Ehrlich Institute (PEI). It was ascertained whether the minimum criteria, recommendations, and extended criteria of the PEI were comprehensibly fulfilled. The number of tests removed from the list by March 2021 was determined. By the closing date of the survey (17.11.2020), the PEI had listed 165 PoC-AgTs that formally fulfilled the minimum criteria and were thus reimbursed. A total of 78 identical systems were identified. Almost all providers were found to have gaps in the information on the validation results of their tests, meaning that an evaluation of performance is only possible to a limited extent. Until March 2021, 25 non-identical PoC-AgTs have been removed from the list. Many PoC-AgTs could not be comprehensively evaluated based on the information provided by the provider. Users are therefore dependent on provider-independent sources of information. © 2021 Mustafa Özcürümez et al., published by De Gruyter, Berlin/Boston.

Biologika bei atopischen Erkrankungen: Indikationsstellung, Nebenwirkungsmanagement und neue Entwicklungen

Mit den Biologika stehen zunehmend mehr Therapeutika zur Verfügung, die zielgerichtet bestimmte Schaltstellen im Pathomechanismus immunologisch dominierter Erkrankungen adressieren. Damit steht mehr die individuelle Krankheitsausprägung des einzelnen Patienten im Fokus der Diagnostik und Therapie (Präzisionsmedizin). Bezüglich der unterschiedlichen Phänotypen atopischer Erkrankungen war das schwere Asthma die erste Entität, für die Biologika zugelassen wurde, gefolgt von Urtikaria, und schließlich der atopischen Dermatitis und der chronischen Rhinosinusitis mit nasalen Polypen. Die Erfahrungen in der Therapie des schweren Asthma bronchiale machten deutlich, dass die Intensität des Ansprechens auf eine Biologikatherapie entscheidend von der Qualität der klinischen und immunologischen Phänotypisierung der Patienten abhängt, wobei diese Unterscheidung z. T. schwierig sein kann und sich verschiedene Phänotypen durchaus überlagern können. Das gilt auch für unterschiedliche Erkrankungen des atopischen Formenkreises, da Patienten in jeweils entsprechend unterschiedlicher Ausprägung unter mehreren atopischen Krankheiten gleichzeitig leiden können. Es bilden sich bereits Biologika heraus, die eine geeignete Therapie für das allergische Asthma bronchiale, das häufig gemeinsam mit einer schweren Neurodermitis auftritt, sowie die chronische Rhinosinusitis mit nasalen Polypen darstellen können. In der Praxis stellt sich dennoch zunehmend die Frage nach möglichen Biologika-Kombinationen zur Therapie komplexer Krankheitsbilder einzelner Patienten. Dabei gilt es, das Nebenwirkungsprofil zu beachten, zu denen auch Hypersensitivitätsreaktionen gehören, deren diagnostisches und logistisches Management eine sichere und effiziente Therapie der Grunderkrankung zum Ziel haben muss. Erhöhte Aufmerksamkeit gilt auch für eine Biologikatherapie bei Schwangerschaften und geplanten (planbaren) Impfungen sowie bestehenden Infektionen, wie zum Beispiel die SARS-CoV-2-Infektion. Vor dem Start einer Biologikatherapie sollten der Immunstatus in Bezug auf chronische Virusund bakterielle Infektionen geprüft und gegebenenfalls vor Therapieeinleitung der Impfstatus aufgefrischt bzw. fehlende Impfungen nachgeholt werden. Derzeit liegen verlässliche Daten zum Effekt von Biologika auf die immunologische Situation der SARS-CoV-2-Infektion und COVID-19 nicht vor. Daher ist die Erforschung und Entwicklung geeigneter Diagnostikverfahren zur Erfassung immunologisch bedingter Nebenwirkungen sowie der Erfassung potenzieller Therapie-Responder und -Non-Responder von großer BedeutungAlternate abstract:With the advent of biologicals, more and more therapeutics are available that specifically address specific switch points in the pathomechanism of immunologically dominated diseases. Thus, the focus of diagnostics and therapy (precision medicine) is more on the individual disease characteristics of the individual patient. Regarding the different phenotypes of atopic diseases, severe asthma was the first entity for which biologicals were approved, followed by urticaria, and finally atopic dermatitis and chronic rhinosinusitis with nasal polyps. Experience in the treatment of severe bronchial asthma has shown that the intensity of the response to biological therapy depends on the quality of clinical and immunological phenotyping of the patients. This also applies to different diseases of the atopic form, as patients can suffer from several atopic diseases at the same time, each with different characteristics. Biologics are already emerging that may represent a suitable therapy for allergic bronchial asthma, which often occurs together with severe neurodermatitis, and chronic rhinosinusitis with nasal polyps. In practice, however, the question of possible combinations of biologicals for the therapy of complex clinical pictures of individual patients is increasingly arising. In doing so, the side effect profile must be taken into account, including hypersensitivity reactions, whose diagnostic and logistical management must aim at a safe and e ficient therapy of the underlying disease. Increased attention must also be paid to biological therapy in pregnancy and planned (predictable) vaccinations as well as existing infections, such as SARS-CoV-2 infection. Before starting a biological therapy, the immune status should be checked with regard to chronic viral and bacterial infections and, if necessary, the vaccination status should be refreshed or missing vaccinations should be made up for before starting therapy. Currently, reliable data on the effect of biologicals on the immunological situation of SARS-CoV-2 infection and COVID-19 are not available. Therefore, research and development of suitable diagnostic methods for detection of immunologically caused side effects as well as detection of potential therapy responders and non-responders is of great importance.